tbuckley/cabot-search huggingface dataset:
Phase II study of dovitinib in first line metastatic or (non resectable primary) adrenocortical carcinoma (ACC): SOGUG study 2011-03.
Authors: Jesús García-Donas, Susana Hernando Polo, Marta Guix, Miguel Angel Climent Duran, María José Méndez-Vidal, Paula Jiménez-Fonseca, Nuria Laínez, Luis Leon Mateos, Fernando Moreno, Eduardo Raul Segura Gonzalez, Ignacio Duran, Francisco Javier Perez, Juan Francisco Rodriguez-Moreno, Sonia Maciá, Sergio Vazquez-Estevez, Jose Angel Arranz, Daniel E. Castellano, Cristina Rodriguez de Antona
Journal: Journal of Clinical Oncology (2014)

4588 Background: Dovitinib is a novel targeted therapy that inhibits the fibroblast growth factor receptor (FGFR). Preclinical studies have pointed to a major role of this pathway in adrenocortical carcinoma (ACC) thus we aimed to test its clinical activity in this tumor. Methods: A phase II proof of concept trial was designed. Based on a two-stage Gehan model 15 patients needed to be included to show a treatment efficacy of at least 15% (probability of Type I error α = 0.05, power [1 – β] = 0.8). Main inclusion criteria was advanced non-resectable ACC, histologically confirmed, with no prior therapy other than mitotane. Primary endpoint was response rate (RR) by RECIST 1.1 centrally assessed. Dovitinib was administered at 500mg daily dose 5 days on 2 days off for 6 months. Continuation of therapy was permitted at physician criteria. A translational substudy looking for biomarkers of efficacy was also scheduled. Results: From January 2012 to August 2012, 17 patients (5 male and 12 female) were included. Median age was 53 years (range 26–72); ECOG was 0–1 in 15 patients, 2 in one patient and N/A in one patient. Grade 3–4 adverse events deemed as related to the drug were: rash (6%), asthenia (12%), diarrhea (6%), GGT elevation (18%), nausea (6%),hypertriglyceridemia (6%), hypertension (6%), hyperkalemia (6%). No toxic death was reported. After a median follow-up of 5.2 months (range 2.27–21) one partial response has been observed. Median PFS was 1.8 months (95%CI [1.35–2.25]), however clinical benefit has been achieved in 30% of patients with long lasting stable disease (>6 months) in 23%. One patient remains on dovitinib 21 months after initiating therapy. We sequenced 409 tumor suppressor genes and oncogenes frequently mutated in cancer (Ion AmpliSeq Comprehensive Cancer Panel) in 9 FFPE tumor samples. Putative variants are currently being validated by Sanger sequencing and will presented at the meeting. Conclusions: Though primary endpoint was not reached, dovitinib showed activity in a subpopulation of ACC patients. The ongoing molecular identification of such subpopulation will be key in order to prompt further investigation. Clinical trial information: NCT01514526.
Early-stage COVID-19 pandemic observations on pulmonary embolism using nationwide multi-institutional data harvesting
Authors: Axel Wismüller, Adora M. DSouza, Anas Z. Abidin, M. Ali Vosoughi, Christopher Gange, Isabel O. Cortopassi, Gracijela Bozovic, Alexander A. Bankier, Kiran Batra, Yosef Chodakiewitz, Yin Xi, Christopher T. Whitlow, Janardhana Ponnatapura, Gary J. Wendt, Eric P. Weinberg, Larry Stockmaster, David A. Shrier, Min Chul Shin, Roshan Modi, Hao Steven Lo, Seth Kligerman, Aws Hamid, Lewis D. Hahn, Glenn M. Garcia, Jonathan H. Chung, Talissa Altes, Suhny Abbara, Anna S. Bader
Journal: npj Digital Medicine (2022)

We introduce a multi-institutional data harvesting (MIDH) method for longitudinal observation of medical imaging utilization and reporting. By tracking both large-scale utilization and clinical imaging results data, the MIDH approach is targeted at measuring surrogates for important disease-related observational quantities over time. To quantitatively investigate its clinical applicability, we performed a retrospective multi-institutional study encompassing 13 healthcare systems throughout the United States before and after the 2020 COVID-19 pandemic. Using repurposed software infrastructure of a commercial AI-based image analysis service, we harvested data on medical imaging service requests and radiology reports for 40,037 computed tomography pulmonary angiograms (CTPA) to evaluate for pulmonary embolism (PE). Specifically, we compared two 70-day observational periods, namely (i) a pre-pandemic control period from 11/25/2019 through 2/2/2020, and (ii) a period during the early COVID-19 pandemic from 3/8/2020 through 5/16/2020. Natural language processing (NLP) on final radiology reports served as the ground truth for identifying positive PE cases, where we found an NLP accuracy of 98% for classifying radiology reports as positive or negative for PE based on a manual review of 2,400 radiology reports. Fewer CTPA exams were performed during the early COVID-19 pandemic than during the pre-pandemic period (9806 vs. 12,106). However, the PE positivity rate was significantly higher (11.6 vs. 9.9%, p < 10-4) with an excess of 92 PE cases during the early COVID-19 outbreak, i.e., ~1.3 daily PE cases more than statistically expected. Our results suggest that MIDH can contribute value as an exploratory tool, aiming at a better understanding of pandemic-related effects on healthcare.
Implication of STAT3 Signaling in Human Colonic Cancer Cells during Intestinal Trefoil Factor 3 (TFF3) – and Vascular Endothelial Growth Factor–Mediated Cellular Invasion and Tumor Growth
Authors: Rivat Christine, Rodrigues Sylvie, Bruyneel Erik, Piétu Geneviève, Robert Amélie, Redeuilh Gérard, Bracke Marc, Gespach Christian, Attoub Samir
Journal: Cancer Research (2005)

Abstract Signal transducer and activator of transcription (STAT) 3 is overexpressed or activated in most types of human tumors and has been classified as an oncogene. In the present study, we investigated the contribution of the STAT3s to the proinvasive activity of trefoil factors (TFF) and vascular endothelial growth factor (VEGF) in human colorectal cancer cells HCT8/S11 expressing VEGF receptors. Both intestinal trefoil peptide (TFF3) and VEGF, but not pS2 (TFF1), activate STAT3 signaling through Tyr705 phosphorylation of both STAT3α and STAT3β isoforms. Blockade of STAT3 signaling by STAT3β, depletion of the STAT3α/β isoforms by RNA interference, and pharmacologic inhibition of STAT3α/β phosphorylation by cucurbitacin or STAT3 inhibitory peptide abrogates TFF- and VEGF-induced cellular invasion and reduces the growth of HCT8/S11 tumor xenografts in athymic mice. Differential gene expression analysis using DNA microarrays revealed that overexpression of STAT3β down-regulates the VEGF receptors Flt-1, neuropilins 1 and 2, and the inhibitor of DNA binding/differentiation (Id-2) gene product involved in the neoplastic transformation. Taken together, our data suggest that TFF3 and the essential tumor angiogenesis regulator VEGF165 exert potent proinvasive activity through STAT3 signaling in human colorectal cancer cells. We also validate new therapeutic strategies targeting STAT3 signaling by pharmacologic inhibitors and RNA interference for the treatment of colorectal cancer patients.
Health and Behavioral Consequences of Binge Drinking in College
Authors: Henry Wechsler
Journal: JAMA (1994)

<h3>Objective.</h3> —To examine the extent of binge drinking by college students and the ensuing health and behavioral problems that binge drinkers create for themselves and others on their campus. <h3>Design.</h3> —Self-administered survey mailed to a national representative sample of US 4-year college students. <h3>Setting.</h3> —One hundred forty US 4-year colleges in 1993. <h3>Participants.</h3> —A total of 17592 college students. <h3>Main Outcome Measures.</h3> —Self-reports of drinking behavior, alcohol-related health problems, and other problems. <h3>Results.</h3> —Almost half (44%) of college students responding to the survey were binge drinkers, including almost one fifth (19%) of the students who were frequent binge drinkers. Frequent binge drinkers are more likely to experience serious health and other consequences of their drinking behavior than other students. Almost half (47%) of the frequent binge drinkers experienced five or more different drinking-related problems, including injuries and engaging in unplanned sex, since the beginning of the school year. Most binge drinkers do not consider themselves to be problem drinkers and have not sought treatment for an alcohol problem. Binge drinkers create problems for classmates who are not binge drinkers. Students who are not binge drinkers at schools with higher binge rates were more likely than students at schools with lower binge rates to experience problems such as being pushed, hit, or assaulted or experiencing an unwanted sexual advance. <h3>Conclusions.</h3> —Binge drinking is widespread on college campuses. Programs aimed at reducing this problem should focus on frequent binge drinkers, refer them to treatment or educational programs, and emphasize the harm they cause for students who are not binge drinkers. (<i>JAMA</i>. 1994;272:1672-1677)
Deaths Attributable to Methadone vs Buprenorphine in France
Authors: Marc Auriacombe
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review
Authors: Giovanni A. Fava, Alessia Gatti, Carlotta Belaise, Jenny Guidi, Emanuela Offidani
Journal: Psychotherapy and Psychosomatics (2015)

Background: Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated. Methods: The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: 'withdrawal symptoms' OR 'withdrawal syndrome' OR 'discontinuation syndrome' OR 'discontinuation symptoms', AND 'SSRI' OR 'serotonin' OR 'antidepressant' OR 'paroxetine' OR 'fluoxetine' OR 'sertraline' OR 'fluvoxamine' OR 'citalopram' OR 'escitalopram'. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014. Results: There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse. Conclusions: Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term 'discontinuation syndrome' that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by 'withdrawal syndrome'. © 2015 S. Karger AG, Basel.
Incidence, Risk Factors, and Outcome of Severe Sepsis and Septic Shock in Adults
Authors: Christian Brun-Buisson
Journal: JAMA (1995)

<h3>Objective.</h3> —To examine the incidence, risk factors, and outcome of severe sepsis in intensive care unit (ICU) patients. <h3>Design and Setting.</h3> —Inception cohort study from a 2-month prospective survey of 11 828 consecutive admissions to 170 adult ICUs of public hospitals in France. <h3>Patients.</h3> —Patients meeting clinical criteria for severe sepsis were included and classified as having documented infection (ie, documented severe sepsis, n=742), or a clinical diagnosis of infection without microbiological documentation (ie, culture-negative severe sepsis, n=310). <h3>Main Outcome Measures.</h3> —Hospital and 28-day mortality after severe sepsis. <h3>Results.</h3> —Clinically suspected sepsis and confirmed severe sepsis occurred in 9.0 (95% confidence interval [CI], 8.5 to 9.5) and 6.3 (95% CI, 5.8 to 6.7) of 100 ICU admissions, respectively. The 28-day mortality was 56% (95% CI, 52% to 60%) in patients with severe sepsis, and 60% (95% CI, 55% to 66%) in those with culture-negative severe sepsis. Major determinants of both early (&lt;3 days) and secondary deaths in the whole cohort were the Simplified Acute Physiology Score (SAPS) II and the number of acute organ system failures. Other risk factors for early death included a low arterial blood pH (&lt;7.33) (<i>P</i>&lt;.001) and shock (<i>P</i>=.03), whereas secondary deaths were associated with the admission category (<i>P</i>&lt;.001), a rapidly or ultimately fatal underlying disease (<i>P</i>&lt;.001), a preexisting liver (<i>P</i>=.01) or cardiovascular (<i>P</i>=.002) insufficiency, hypothermia (<i>P</i>=.02), thrombocytopenia (<i>P</i>=.01), and multiple sources of infection (<i>P</i>=.02). In patients with documented sepsis, bacteremia was associated with early mortality (<i>P</i>=.03). <h3>Conclusions.</h3> —Only three of four patients presenting with clinically suspected severe sepsis have documented infection. However, patients with clinically suspected sepsis but without microbiological documentation and patients with documented infection share common risk factors and are at similarly high risk of death. In addition to the severity of illness score, acute organ failures and the characteristics of underlying diseases should be accounted for in stratification of patients and outcome analyses. (<i>JAMA</i>. 1995;274:968-974)
A Commentary on “The minimum number of examined lymph nodes for accurate nodal staging and optimal survival of stage T1-2 esophageal squamous cell carcinoma: A retrospective multicenter cohort with SEER database validation” [Int. J. Surg. (2022) 104 106764]
Authors: Yi-Min Gu, Si-Mian Lyu, Guo-Wei Che
Journal: International Journal of Surgery (2022)
Economic evaluation of laboratory diagnostic test types in Covid-19 epidemic: A systematic review
Authors: Zeinab Dolatshahi, Shahin Nargesi, Jamil Sadeghifar, Fateme Mezginejad, Abdosaleh Jafari, Mohammad Bazyar, Sobhan Ghafourian, Nadia Sani'ee
Journal: International Journal of Surgery (2022)
STAMP: Simultaneous Training and Model Pruning for low data regimes in medical image segmentation
Authors: Nicola K. Dinsdale, Mark Jenkinson, Ana I.L. Namburete
Journal: Medical Image Analysis (2022)

Acquisition of high quality manual annotations is vital for the development of segmentation algorithms. However, to create them we require a substantial amount of expert time and knowledge. Large numbers of labels are required to train convolutional neural networks due to the vast number of parameters that must be learned in the optimisation process. Here, we develop the STAMP algorithm to allow the simultaneous training and pruning of a UNet architecture for medical image segmentation with targeted channelwise dropout to make the network robust to the pruning. We demonstrate the technique across segmentation tasks and imaging modalities. It is then shown that, through online pruning, we are able to train networks to have much higher performance than the equivalent standard UNet models while reducing their size by more than 85% in terms of parameters. This has the potential to allow networks to be directly trained on datasets where very low numbers of labels are available.
Transient secretion of VEGF protein from transplanted hiPSC-CMs enhances engraftment and improves rat heart function post MI
Authors: Xuefeng Ai, Bingqian Yan, Nevin Witman, Yiqi Gong, Li Yang, Yao Tan, Ying Chen, Minglu Liu, Tingting Lu, Runjiao Luo, Huijing Wang, Kenneth R. Chien, Wei Wang, Wei Fu
Journal: Molecular Therapy (2022)

Cell-based therapies offer an exciting and novel treatment for heart repair following myocardial infarction (MI). However, these therapies often suffer from poor cell viability and engraftment rates, which involve many factors, including the hypoxic conditions of the infarct environment. Meanwhile, vascular endothelial growth factor (VEGF) has previously been employed as a therapeutic agent to limit myocardial damage and simultaneously induce neovascularization. This study took an approach to transiently overexpress VEGF protein, in a controlled manner, by transfecting human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with VEGF mRNA prior to transplantation. The conditioning of iPSC-CMs with VEGF mRNA ultimately led to greater survival rates of the transplanted cells, which promoted a stable vascular network in the grafted region. Furthermore, bulk RNA transcriptomics data and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) and AGE-RAGE signaling pathways were significantly upregulated in the VEGF-treated iPSC-CMs group. The over-expression of VEGF from iPSC-CMs stimulated cell proliferation and partially attenuated the hypoxic environment in the infarcted area, resulting in reduced ventricular remodeling. This study provides a valuable solution for the survival of transplanted cells in tissue-engineered heart regeneration and may further promote the application of modified mRNA (modRNA) in the field of tissue engineering.
AAV and hepatitis: Cause or coincidence?
Authors: Ype P. de Jong, Roland W. Herzog
Journal: Molecular Therapy (2022)

Adeno-associated viral (AAV) vectors are widely used in clinical gene therapy and, in particular, in applications based on in vivo gene transfer. These recombinant vectors are derived from wild-type AAVs, which are replication incompetent viruses that depend on other viruses, such as adenoviruses (AdVs) or herpes viruses, to complete their lytic replication cycle. Various serotypes, including AAV2, infect the majority of people around the world and are thought to be part of self-limiting respiratory infections without chronic morbidity or mortality. Because of this benign clinical profile, AAV vectors are generally referred to as nonpathogenic viruses. After initially having been associated with a subset of hepatocellular carcinomas (HCCs), two recent clinical investigations further challenge its nonpathogenic nature and report the surprising finding that all explanted livers from children with acute severe hepatitis contained high levels of AAV2. This raises the question of whether AAV could contribute to hepatitis during co-infection with a helper virus.
Intravenous treatment with a molecular chaperone designed against β-amyloid toxicity improves Alzheimer’s disease pathology in mouse models
Authors: Shaffi Manchanda, Lorena Galan-Acosta, Axel Abelein, Simone Tambaro, Gefei Chen, Per Nilsson, Jan Johansson
Journal: Molecular Therapy (2022)

Attempts to treat Alzheimer's disease with immunotherapy against the β-amyloid (Aβ) peptide or with enzyme inhibitors to reduce Aβ production have not yet resulted in effective treatment, suggesting that alternative strategies may be useful. Here we explore the possibility of targeting the toxicity associated with Aβ aggregation by using the recombinant human (rh) Bri2 BRICHOS chaperone domain, mutated to act selectively against Aβ42 oligomer generation and neurotoxicity in vitro. We find that treatment of Aβ precursor protein (App) knockin mice with repeated intravenous injections of rh Bri2 BRICHOS R221E, from an age close to the start of development of Alzheimer's disease-like pathology, improves recognition and working memory, as assessed using novel object recognition and Y maze tests, and reduces Aβ plaque deposition and activation of astrocytes and microglia. When treatment was started about 4 months after Alzheimer's disease-like pathology was already established, memory improvement was not detected, but Aβ plaque deposition and gliosis were reduced, and substantially reduced astrocyte accumulation in the vicinity of Aβ plaques was observed. The degrees of treatment effects observed in the App knockin mouse models apparently correlate with the amounts of Bri2 BRICHOS detected in brain sections after the end of the treatment period.
Effectiveness of Switching From Intravenous to Subcutaneous Infliximab in Patients With Inflammatory Bowel Diseases: the REMSWITCH Study
Authors: Anthony Buisson, Maria Nachury, Maud Reymond, Clara Yzet, Pauline Wils, Laure Payen, Marie Laugie, Luc Manlay, Nicolas Mathieu, Bruno Pereira, Mathurin Fumery
Journal: Clinical Gastroenterology and Hepatology (2022)
Clinical and Echocardiographic Characteristics of Flow-Based Classification Following Balloon-Expandable Transcatheter Heart Valve in PARTNER Trials
Authors: Oludamilola Akinmolayemi, Denizhan Ozdemir, Philippe Pibarot, Yanglu Zhao, Jonathon Leipsic, Pamela S. Douglas, Wael A. Jaber, Neil J. Weissman, Philipp Blanke, Rebecca T. Hahn
Journal: JACC. Cardiovascular imaging (2022)
Effect of Immunosuppressive Therapy and Biopsy Status in Monitoring Therapy Response in Suspected Cardiac Sarcoidosis
Authors: Chaitanya Rojulpote, Abhijit Bhattaru, Christopher Jean, Sarah L. Adams, Vandan Patel, Mahesh K. Vidula, Senthil Selvaraj, Jacob Dubroff, Eliot Peyster, Caitlin B. Clancy, Karen Patterson, Francis E. Marchlinski, Milton Rossman, Lee Goldberg, Paco E. Bravo
Journal: JACC. Cardiovascular imaging (2022)
ΔNp63α Up-Regulates the <i>Hsp70</i> Gene in Human Cancer
Authors: Guojun Wu, Motonobu Osada, Zhongmin Guo, Alexey Fomenkov, Shahnaz Begum, Ming Zhao, Sunil Upadhyay, Mingzhao Xing, Feng Wu, Chulso Moon, William H. Westra, Wayne M. Koch, Roberto Mantovani, Joseph A. Califano, Edward Ratovitski, David Sidransky, Barry Trink
Journal: Cancer Research (2005)

Abstract HSP70, a stress response protein, is known to be a determinant of cell death and cell transformation. We show that different isoforms of p63 have different transcriptional activities on hsp70 genes. ΔNp63α, an abundantly expressed isoform of p63, activates (in vitro and in vivo), whereas TAp63γ down-regulates the expression of hsp70. We further show that the transactivation domain at the NH2 terminus of p63 represses, whereas the COOH terminus activates hsp70 transcription. In addition, ΔNp63α regulates transcription of the hsp70 gene through its interaction with the CCAAT binding factor and NF-Y transcription factors which are known to form a complex with the CCAAT box located in the hsp70 promoter. Moreover, ΔNp63α expression correlates with HSP70 expression in all head and neck cancer cell lines. Finally, we show colocalization of ΔNp63α and HSP70 in the epithelium and coexpression of both proteins in 41 primary head and neck cancers. Our study provides strong evidence for the physiologic association between ΔNp63α and hsp70 in human cancer, thus further supporting the oncogenic potential of ΔNp63α.